Genetic Variant MYC:c.-342C>T (chr8-127736252-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4BA1

The NM_002467.6(MYC):c.-342C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0319 in 531,178 control chromosomes in the GnomAD database, including 639 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.030 ( 148 hom., cov: 32)

Exomes 𝑓: 0.033 ( 491 hom. )

Consequence

MYC
NM_002467.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.92

Publications

21 publications found

Variant links:

COSMIC-nc: COSV52368217

Genes affected

MYC (HGNC:7553): (MYC proto-oncogene, bHLH transcription factor) This gene is a proto-oncogene and encodes a nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation. The encoded protein forms a heterodimer with the related transcription factor MAX. This complex binds to the E box DNA consensus sequence and regulates the transcription of specific target genes. Amplification of this gene is frequently observed in numerous human cancers. Translocations involving this gene are associated with Burkitt lymphoma and multiple myeloma in human patients. There is evidence to show that translation initiates both from an upstream, in-frame non-AUG (CUG) and a downstream AUG start site, resulting in the production of two isoforms with distinct N-termini. [provided by RefSeq, Aug 2017]

MYC links:

CASC11 (HGNC:48939): (cancer susceptibility 11)

CASC11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.1).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYC	NM_002467.6 link	c.-342C>T		5_prime_UTR_variant	Exon 1 of 3	ENST00000621592.8	NP_002458.2	P01106-2
MYC	NM_001354870.1 link	c.-342C>T		5_prime_UTR_variant	Exon 1 of 3		NP_001341799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYC	ENST00000621592.8 link	c.-342C>T		5_prime_UTR_variant	Exon 1 of 3	1	NM_002467.6	ENSP00000478887.2		P01106-2

Frequencies

GnomAD3 genomes

AF:

0.0300

AC:

4560

AN:

152170

Hom.:

149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0191

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0668

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.0879

Gnomad FIN

AF:

0.00885

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0203

Gnomad OTH

AF:

0.0211

GnomAD4 exome

AF:

0.0327

AC:

12396

AN:

378890

Hom.:

491

Cov.:

AF XY:

0.0346

AC XY:

6819

AN XY:

196966

show subpopulations

African (AFR)

AF:

0.0196

AC:

212

AN:

10834

American (AMR)

AF:

0.0387

AC:

494

AN:

12752

Ashkenazi Jewish (ASJ)

AF:

0.0125

AC:

152

AN:

12194

East Asian (EAS)

AF:

0.136

AC:

3813

AN:

28008

South Asian (SAS)

AF:

0.0819

AC:

2327

AN:

28398

European-Finnish (FIN)

AF:

0.0116

AC:

316

AN:

27170

Middle Eastern (MID)

AF:

0.00572

AC:

AN:

1748

European-Non Finnish (NFE)

AF:

0.0192

AC:

4515

AN:

235020

Other (OTH)

AF:

0.0245

AC:

557

AN:

22766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

778

1556

2335

3113

3891

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0300

AC:

4563

AN:

152288

Hom.:

148

Cov.:

AF XY:

0.0331

AC XY:

2468

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0190

AC:

789

AN:

41560

American (AMR)

AF:

0.0670

AC:

1026

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

AN:

3472

East Asian (EAS)

AF:

0.143

AC:

741

AN:

5166

South Asian (SAS)

AF:

0.0878

AC:

424

AN:

4830

European-Finnish (FIN)

AF:

0.00885

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0203

AC:

1380

AN:

68018

Other (OTH)

AF:

0.0208

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

221

442

663

884

1105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0227

Hom.:

305

Bravo

AF:

0.0304

Asia WGS

AF:

0.0920

AC:

319

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

1.9

PromoterAI

0.0074

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.3

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over